EFFECTS OF EPIDERMAL GROWTH-FACTOR (EGF), PLATELET-DERIVED GROWTH-FACTOR (PDGF) AND FIBROBLAST GROWTH-FACTOR (FGF) ON HUMAN ADIPOCYTE DEVELOPMENT AND FUNCTION

We investigated the effects of epidermal growth factor (EGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) on the differentiation of human adipocyte precursor cells and some metabolic aspects of newly formed fat cells kept in primary culture. Exposure of stromal cells from human adipose tissue to EGF (0.1-100 ng mL(-1)) resulted in a dose- and time-dependent decrease in the number of developing fat cells and the activity of glycerol-3-phosphate dehydrogenase (GPDH), a marker of adipose differentiation. Continuous presence of EGF completely blocked lipid accumulation with a ED(50) in the range of 0.2 ng mL(-1). This inhibitory action of EGF was associated with a potent stimulation of cell proliferation, up to 8-fold compared with cultures in the absence of EGF.PDGF (0.1-50 ng mL(-1)) and FGF (0.1-100 ng mL(-1)) provoked a less marked suppression of GPDH activities which was significant at concentrations of 10 ng mL(-1) and higher. A 12 day exposure to EGF of differentiated cells was followed by a suppression of GPDH and, again, a significant increase in cell number. Concomitantly, a distinct loss of cellular lipids was observed in the newly formed adipocytes. This effect could be partly explained by a stimulation of lipolysis, since EGF caused an increase of glycerol in the culture medium. Addition of PDGF or FGF to newly developed fat cells had no effect on lipolysis but, at higher concentrations, also decreased GPDH activity. These findings suggest that EGF is a potent inhibitor of adipose cell differentiation at physiological concentrations, and may be involved in the control of human adipose tissue development and function.